| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Immunology,* The Scripps Research Institute, La Jolla; and the Department of Thoracic Surgery, Scripps Clinic, La Jolla, California
The endothelial surface of atherosclerotic lesions of ApoE knockout mice was interrogated by in vivo biopanning with a phage-displayed constrained peptidyl library. Through repeated biopanning, 103 peptidyl sequences were identified, many are homologous to known proteins. The sequence CAPGPSKSC contains motifs that are shared by 9.7% of selected peptides. On phage or as a synthetic peptide, this constrained peptide selectively bound to atherosclerotic lesion surfaces of ApoE knockout mice in vivo and of human atherosclerotic lesions ex vivo. A cell-surface protein of 
82 kd recognized by this peptide was affinity-purified and determined by mass spectrometry analysis as glucose-regulated protein 78 (Grp78), indicating the surprising presence of this endoplasmic reticulum chaperone on the endothelial cell surface of atherosclerotic lesions. Peptides that mimicked binding functions of their homologues were demonstrated with three peptides homologous to tissue inhibitor of metalloproteinase-2 (TIMP-2), ie, CNHRYMQMC, CNQRHQMSC, and CNNRSDGMC. Phage carrying CNHRYMQMC bound to atherosclerotic lesion endothelium of ApoE knockout mice in vivo. The three peptides bound to endothelial cells in a dose-dependent manner and were inhibited by TIMP-2 protein. These peptides provide a set of probes to interrogate the cell surface repertoire associated with atherogenesis and thrombotic complications.
This article has been cited by other articles:
 |
|
 |
|
  G. Bhattacharjee, J. Ahamed, R. Pawlinski, C. Liu, N. Mackman, W. Ruf, and T. S. Edgington Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1 Circ. Res., February 29, 2008; 102(4): 457 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A.H. Jarvinen and E. Ruoslahti Molecular Changes in the Vasculature of Injured Tissues Am. J. Pathol., August 1, 2007; 171(2): 702 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Abstracts Heart, June 1, 2007; 93(suppl_1): A5 - A105. [Full Text] [PDF]
|
|
|
|
 |
|
 R. Robert, M.-J. Jacobin-Valat, D. Daret, S. Miraux, A. T. Nurden, J.-M. Franconi, and G. Clofent-Sanchez Identification of Human scFvs Targeting Atherosclerotic Lesions: SELECTION BY SINGLE ROUND IN VIVO PHAGE DISPLAY J. Biol. Chem., December 29, 2006; 281(52): 40135 - 40143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nahrendorf, F. A. Jaffer, K. A. Kelly, D. E. Sosnovik, E. Aikawa, P. Libby, and R. Weissleder Noninvasive Vascular Cell Adhesion Molecule-1 Imaging Identifies Inflammatory Activation of Cells in Atherosclerosis Circulation, October 3, 2006; 114(14): 1504 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zhang, J. A. Hoffman, and E. Ruoslahti Molecular Profiling of Heart Endothelial Cells Circulation, September 13, 2005; 112(11): 1601 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Pozza and R. C. Austin Getting a GRP on Tissue Factor Activation Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1529 - 1531. [Full Text] [PDF]
|
|
|
|
|
|
G. Bhattacharjee, J. Ahamed, B. Pedersen, A. El-Sheikh, N. Mackman, W. Ruf, C. Liu, and T. S. Edgington Regulation of Tissue Factor-Mediated Initiation of the Coagulation Cascade by Cell Surface Grp78 Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1737 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Kelly, J. R. Allport, A. Tsourkas, V. R. Shinde-Patil, L. Josephson, and R. Weissleder Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle Circ. Res., February 18, 2005; 96(3): 327 - 336. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
